1. Field of Invention
The present invention relates to compounds and compositions for modulating immunological responses and, more specifically, to compounds and compositions for up-regulating HLA-DM activity. The invention also relates to assays and kits.
2. Discussion of Related Art
The invariant HLA-DM molecule in humans is involved in loading peptides onto MHC class II molecules. It is encoded in the MHC within a set of genes resembling MHC class II genes. A homologous protein in mice is called H-2M.
HLA-DM is a molecule that may act as a catalyst for peptide exchange by positively selecting peptides with a high affinity for MHC class II. In some instances, an increase or decrease in HLA-DM activity may be beneficial in disease treatment. For example, a subject exhibiting symptoms of, or predisposed to, certain autoimmune diseases may benefit from a decrease in HLA-DM activity. Alternatively, a subject exhibiting symptoms of, or a predisposition to, an infection or a cancer may benefit from increased HLA-DM activity. Likewise, a subject may benefit from an increase in HLA-DM activity in response to a disease that downregulates HLA-DM.
HLA-DM may also act as a peptide editor by positively selecting peptides having a high affinity for MHC class II. Acceleration of the catalytic exchange of peptides may increase high affinity peptides and/or decrease low affinity peptides displayed on the surface of antigen presenting cells. As it is believed that high affinity peptides are more immunogenic than are low affinity peptides, a change (e.g., an increase) in the ratio of high affinity to low affinity peptides may improve a subject's immune response to a pathogen.
It would be desirable to have compounds that could influence HLA-DM activity and, hence, the immune response.